Is MET p.Glu906= (c.2718G>A) pathogenic?

MET p.Glu906= (c.2718G>A) is classified Benign/Likely benign in MET (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-12). Very rare (popmax 0.0011%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with MET p.Glu906= (c.2718G>A)?

MET p.Glu906= (c.2718G>A) is associated with hereditary neoplastic syndrome, renal cell carcinoma (ClinVar).

How common is MET p.Glu906= (c.2718G>A) in the general population?

MET p.Glu906= (c.2718G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

MET p.Glu906=

c.2718G>A · rs752013993 · VCV524898

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP -0.36, phastCons 1
Overall
CADD	7.976	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,066 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000342% 5/1,461,568 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,066
European (non-Finnish)	0.000339%	294,954

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MET
Protein: p.Glu906=
Coding: c.2718G>A
MANE Select: NM_024755 · reported on NM_000245
dbSNP: rs752013993
Type: single nucleotide variant
Location: chr7:116769779 (GRCh38)
Structure: AlphaFold pLDDT 52.38
Residue 906: the 'disordered' region

Full MET gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: renal cell carcinoma

Similar variants

MET p.Glu906Lys Uncertain significance ★★ ⚠ same residue
MET p.Glu906Asp Uncertain significance ★ ⚠ same residue
MET p.Glu906Gly Uncertain significance ★ ⚠ same residue
MET p.His1094Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
MET p.Met1131Thr Pathogenic/Likely pathogenic ★★ same condition
MET p.Val1092Ile Pathogenic/Likely pathogenic ★★ same condition
MET p.Val1220Ile Pathogenic/Likely pathogenic ★★ ⚠ same condition
MET c.1200+2T>C Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/met-p-glu906 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown